Aldosterone is important in sodium homeostasis in normal and hypertensive subjects. We have previously identified three areas where significant questions remain unanswered and have proceeded to investigate them in a methodical fashion: 1. There is now direct evidence for an Aldosterone Stimulating Glycoprotein (ASG) in the urine of normal and hypertensive subjects. We have used an in vitro isolated adrenal glomerulosa cell incubation system to confirm the presence of this material and have made studies of its mechanism of action. We propose to collect, purify and characterize this material and to perform biochemical and physiological studies to determine its importance in man. 2. We have studied the interaction of more than 60 steroids with the renal cytosol mineralocorticoid receptors. Additional studies of the interaction of progesterone with selected mineralocorticoids stongly suggest that it may serve as an important natural antagonist to sodium retention in man. We have demonstrated this potential in DOCA treated rats. We are extending our studies of mineralocorticoid interactions to selected subgroups of hypertensive patients and will evaluate the response of the adrenal biosynthetic pathway to ACTH and methrapone in order to determine whether latent abnormalities are present in man. 3. We have demonstrated a close relationship between the effect of aldosterone upon sodium transport and uptake of 14C-riboflavin into renal flavin nucleotides. Administration of riboflavin antagonists blocks sodium but not potassium transport and 14C-riboflavin uptake into the kidney. We are planning to examine the effects of these analogs upon experimental mineralocorticoid hypertension in the rat and to continue our biochemical investigation of the effects of aldosterone upon flavoprotein dependent enzymes.